Protein degradation mechanisms that regulate daily and seasonal timing

Project Summary/Abstract The circadian clock is necessary to synchronize biological processes with daily changes in the environment, but it is also required for organisms to measure photoperiod (daylength) and align physiology with the seasons. Rapid progress has been made in understanding the transcriptional connections that drive daily and seasonal timing. We know less about how post-translational mechanisms, such as protein degradation regulate the circadian clock and seasonal timing. Plants, such as Arabidopsis, have served as preeminent model systems for understanding the circadian clock, and in particular, how the circadian clock mediates photoperiod measurement. In the period of funding from the previous MIRA award, my laboratory has worked at the interface of protein degradation and the circadian clock, discovering protein degradation mechanisms that regulate the circadian clock and seasonal physiology. During the funding period, we also discovered that one of the E3 ubiquitin ligases in our study is controlled by a non-canonical photoperiod measurement system in plants, opening a new, but complementary, avenue of research in our lab. Our future work will build on these foundational studies by addressing two major goals 1) performing detailed investigations of three E3 ubiquitin ligase families that control important clock output processes and 2) continuing to identify and study non-canonical photoperiod measurement systems in plants. These studies will uncover general principles about how the circadian clock controls daily and seasonal biology. The circadian clock regulates fundamental biological processes in many organisms, and clock dysfunction increases the prevalence of human disease and mood disorders. Thus, the work that we perform will have far- reaching impacts and fits the goals of NIGMS because: 1) it will provide basic principles and molecular logic for eukaryotic circadian clock systems, 2) it will provide a more comprehensive understanding of the post- translational mechanisms that overlay transcriptional feedback loops of clocks, and 3) it will serve as a framework for similar studies in other eukaryotic timing systems, including humans.